Bottom Line:
Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs.Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype.Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo.

ABSTRACTBeside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT), commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR) are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs). In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR(1) and 5-HTR(2) receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR(3), 5-HTR(4) and 5-HTR(7) receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders.

pone-0006453-g002: 5-HT inhibits the release of IP 10/CXCL10 and stimulates MDC/CCL22 secretion in DCs.Immature and mature DCs were left untreated or were stimulated with the indicated concentration of 5-HT for 24 h (A–B). CXCL10 and CCL22 release was measured by ELISA. The results are expressed as mean pg/ml±SEM (n = 4).

Mentions:
Immature DCs produce high levels of CCL22/MDC and very low levels of IP-10/CXCL10, whereas in LPS-matured DCs the secretion of both CCL22 and CXCL10 is up-regulated (Fig. 2). When DCs were treated with LPS in the presence of 5-HT, a dose dependent inhibition of CXCL10 production was observed (Fig. 2A), while the production of CCL22 was increased. In addition 5-HT also enhanced the secretion of CCL22 in immature DCs (Fig. 2B).

pone-0006453-g002: 5-HT inhibits the release of IP 10/CXCL10 and stimulates MDC/CCL22 secretion in DCs.Immature and mature DCs were left untreated or were stimulated with the indicated concentration of 5-HT for 24 h (A–B). CXCL10 and CCL22 release was measured by ELISA. The results are expressed as mean pg/ml±SEM (n = 4).

Mentions:
Immature DCs produce high levels of CCL22/MDC and very low levels of IP-10/CXCL10, whereas in LPS-matured DCs the secretion of both CCL22 and CXCL10 is up-regulated (Fig. 2). When DCs were treated with LPS in the presence of 5-HT, a dose dependent inhibition of CXCL10 production was observed (Fig. 2A), while the production of CCL22 was increased. In addition 5-HT also enhanced the secretion of CCL22 in immature DCs (Fig. 2B).

Bottom Line:
Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs.Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype.Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo.

ABSTRACTBeside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT), commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR) are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs). In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR(1) and 5-HTR(2) receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR(3), 5-HTR(4) and 5-HTR(7) receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders.